Ciliary neurotrophic factor (CNTF) genotypes: influence on choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) activities and neurotrophin 3 (NT3) concentration in human post mortem brain tissue.
Cell culture and animal models suggest a significant influence of ciliary neurotrophic factor (CNTF) on cholinergic neurotransmitter systems. We therefore conducted an explorative pilot study to investigate the influence of a null mutation allele of the CNTF gene on ChAT (choline acetyltransferase) and AChE (acetylcholine esterase) activities in various regions of human post mortem brain tissue. Additionally, we determined NT3 (neurotrophin 3) levels, a factor which exhibits neurotrophic properties at cholinergic neurons, and the concentration of which in these brain regions varies with CNTF genotype. Homozygous carriers of the mutation lack CNTF completely, whereas heterozygotes have a CNTF level which is about half that of non-carriers. There was a trend toward lower ChAT and AChE activity levels in the cingulate cortex in individuals homozygous or heterozygous for the mutation when compared with non-mutant individuals. Additionally, higher NT3 concentrations were found in this region, as well as in the frontal cortex and caudate nucleus. ChAT and AChE activities in the frontal cortex and caudate nucleus were not significantly linked to CNTF genotype. These results are, however, preliminary and need to be further explored. The individuals investigated were heterogenous with respect to a range of parameters; nevertheless, the hypothesis that genetic variants for neurotrophic factors play a role in diseases of neural development and plasticity deserves further examination.
Thome
J
J
Department of Psychiatry, University of Würzburg, Germany. nerk113@rzbox.uni-wuerzburg.de
Nara
K
K
Foley
P
P
Michel
T
T
Gsell
W
W
Retz
W
W
Rosler
M
M
Riederer
P
P
D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D000375:Aging / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D020933:Neurotrophin 3
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D004247:DNA; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase